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Defining variant-resistant epitopes targeted by SARS-CoV-2 antibodies: A global consortium study.


ABSTRACT: Antibody-based therapeutics and vaccines are essential to combat COVID-19 morbidity and mortality after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Multiple mutations in SARS-CoV-2 that could impair antibody defenses propagated in human-to-human transmission and spillover or spillback events between humans and animals. To develop prevention and therapeutic strategies, we formed an international consortium to map the epitope landscape on the SARS-CoV-2 spike protein, defining and structurally illustrating seven receptor binding domain (RBD)–directed antibody communities with distinct footprints and competition profiles. Pseudovirion-based neutralization assays reveal spike mutations, individually and clustered together in variants, that affect antibody function among the communities. Key classes of RBD-targeted antibodies maintain neutralization activity against these emerging SARS-CoV-2 variants. These results provide a framework for selecting antibody treatment cocktails and understanding how viral variants might affect antibody therapeutic efficacy.

SUBMITTER: Hastie KM 

PROVIDER: S-EPMC9302186 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature

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Defining variant-resistant epitopes targeted by SARS-CoV-2 antibodies: A global consortium study.

Hastie Kathryn M KM   Li Haoyang H   Bedinger Daniel D   Schendel Sharon L SL   Dennison S Moses SM   Li Kan K   Rayaprolu Vamseedhar V   Yu Xiaoying X   Mann Colin C   Zandonatti Michelle M   Diaz Avalos Ruben R   Zyla Dawid D   Buck Tierra T   Hui Sean S   Shaffer Kelly K   Hariharan Chitra C   Yin Jieyun J   Olmedillas Eduardo E   Enriquez Adrian A   Parekh Diptiben D   Abraha Milite M   Feeney Elizabeth E   Horn Gillian Q GQ   Aldon Yoann Y   Ali Hanif H   Aracic Sanja S   Cobb Ronald R RR   Federman Ross S RS   Fernandez Joseph M JM   Glanville Jacob J   Green Robin R   Grigoryan Gevorg G   Lujan Hernandez Ana G AG   Ho David D DD   Huang Kuan-Ying A KA   Ingraham John J   Jiang Weidong W   Kellam Paul P   Kim Cheolmin C   Kim Minsoo M   Kim Hyeong Mi HM   Kong Chao C   Krebs Shelly J SJ   Lan Fei F   Lang Guojun G   Lee Sooyoung S   Leung Cheuk Lun CL   Liu Junli J   Lu Yanan Y   MacCamy Anna A   McGuire Andrew T AT   Palser Anne L AL   Rabbitts Terence H TH   Rikhtegaran Tehrani Zahra Z   Sajadi Mohammad M MM   Sanders Rogier W RW   Sato Aaron K AK   Schweizer Liang L   Seo Jimin J   Shen Bingqing B   Snitselaar Jonne L JL   Stamatatos Leonidas L   Tan Yongcong Y   Tomic Milan T MT   van Gils Marit J MJ   Youssef Sawsan S   Yu Jian J   Yuan Tom Z TZ   Zhang Qian Q   Peters Bjoern B   Tomaras Georgia D GD   Germann Timothy T   Saphire Erica Ollmann EO  

Science (New York, N.Y.) 20210923 6566


Antibody-based therapeutics and vaccines are essential to combat COVID-19 morbidity and mortality after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Multiple mutations in SARS-CoV-2 that could impair antibody defenses propagated in human-to-human transmission and spillover or spillback events between humans and animals. To develop prevention and therapeutic strategies, we formed an international consortium to map the epitope landscape on the SARS-CoV-2 spike protein, d  ...[more]

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